SEE THE SYMPTOMS AND DIAGNOSIS JOURNEYS OF REAL PATIENTS WITH XLH

  • 18-19 months: pediatric evaluation
    • 18-month-old female presented with leg bowing, wide-based gait, delayed walking, and poor growth; fear of climbing stairs
    • X-rays: indicative of metaphyseal dysplasia
    • Other clinical findings: strabismus, suspected to contribute to walking delay; underwent strabismus surgery
  • 28 months: orthopedic evaluation
    • Physical exam: short stature, height less than 5th percentile since age 15 months (See Growth Chart); worsened bowing and waddling gait
    • X-rays: significant bilateral genu varum with mild beaking and sloping of the proximal tibial metaphysis; metaphyseal-diaphyseal angles of bilateral proximal tibiae measured 16 degrees; bilateral irregularity of the distal femoral metaphysis also noted; femoral heads were normally located
    • Differential diagnosis: possible Blount’s disease, metaphyseal dysplasia, or physiologic genu varum
  • 29 months: genetics evaluation
    • No family history of bone disease
    • Suspected diagnosis: metaphyseal dysplasia
    • Underwent genetic testing for Schmid metaphyseal chondrodysplasia and Shwachman-Diamond syndrome; results were negative for pathologic variants
    • Diagnosis: unknown, referred to skeletal dysplasia clinic
  • 31 months: endocrinology evaluation
    • Physical exam: bilateral genu varum
    • X-rays: bilateral mild coxa vara, tibial varus (left greater than right) with metaphyseal irregularity and fraying of the distal femur, tibia, and ulna; metaphyseal widening at wrists
    • Laboratory findings (See Table)
    • Other findings: 2nd percentile for weight; 1st percentile for height (See Growth Chart)

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Growth Chart
Growth chart for 56-month-old patient with XLH
History of growth progression. Patient had short stature. At 31 months, patient was in the 1st percentile for height.
The reference percentiles on the graph are combined from the two clinical growth charts for girls 2-20 years of age provided by the Centers for Disease Control and Prevention.
  • Hypophosphatemic rickets; positive for PHEX mutation; negative in parents – spontaneous X-linked hypophosphatemia (XLH)
  • Treatment: oral calcitriol and potassium phosphate
  • 39 months: nephrology follow-up evaluation
    • Patient continued to take oral calcitriol and potassium phosphate
    • Physical exam: wide-based gait; mild genu varum; intercondylar distance 1.0 cm; bilateral mild tibial bowing
    • X-rays: mild metaphyseal fraying at distal radius and ulna; metaphyseal widening and fraying at distal femur and proximal tibia (See X-rays 1-3)
  • 54 months: further management options explored due to continued disease progression
  • Laboratory findings (See Table)

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X-ray 1: Right Wrist
Wrist X-ray of 56-month-old patient with XLH

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X-ray 2: Knees
Knees X-ray of 56-month-old patient with XLH

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X-ray 3: Legs
Legs X-ray of 56-month-old patient with XLH

54 months: Mild metaphyseal fraying at the bilateral distal radius and ulna and to a lesser extent of the bilateral distal femoral metaphyses.

Test (referencea range unit) Results – 31 months Results – 54 months
Serum phosphorus (4.3-6.8 mg/dL) 2.9 2.5
TmP/GFR (4.0-5.2 mg/dL) 2.4 n/a
25(OH)D (≥20 ng/mL) 41 31
ALP (<156-369 U/L) 461 404
Serum calcium (9.2-10.5 mg/dL) 9.4 9.9
PTH (<10-65 pg/mL) 57 31

25(OH)D, 25-hydroxyvitamin D; ALP, alkaline phosphatase; PTH, parathyroid hormone; TmP/GFR, ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate; ULN, upper limit of normal.

 

aIndicates normal range, age, and sex matched. Note that normal range values may vary depending on reference dataset. The ranges in this table were provided by the treating physician.

56-month-old female case summary timeline
  • Although the patient was seen by multiple specialists, a conclusive diagnosis was not reached over a period of 13 months, after referral to an endocrinologist; the patient was subsequently followed by a nephrologist
    • For patients with XLH, the diagnosis process can be long and laborious, and proper specialist referral can be key to early disease management
  • This patient’s disease symptoms continued to progress despite therapy with oral calcitriol and potassium phosphate

*The information for this case study was provided courtesy of Dr. Anthony Portale, Director of the Pediatric Dialysis Program, UCSF Benioff Children’s Hospital, San Francisco. This case study represents a real patient and is intended to be illustrative, not a recommendation for treatment or management. This case study does not claim to represent typical results.

Reference:

1. Centers for Disease Control and Prevention. Clinical growth charts. 2 to 20 years: girls. Centers for Disease Control and Prevention. Published May 30, 2000. Accessed March 14, 2022. https://www.cdc.gov/growthcharts/data/set2clinical/cj41c072.pdf